RESUMO
OBJECTIVE: To determine the interobserver reproducibility of fetal ultrasound biometric and amniotic-fluid measurements in the third trimester of pregnancy, according to maternal body mass index (BMI) category. METHODS: This was a prospective cohort study of women with a singleton gestation beyond 34 weeks, recruited into four groups according to BMI category: normal (18.0-24.9 kg/m2 ), overweight (25.0-29.9 kg/m2) , obese (30.0-39.9 kg/m2 ) and morbidly obese (≥ 40 kg/m2 ). Multiple pregnancies, women with diabetes and pregnancies with a fetal growth, structural or genetic abnormality were excluded. In each woman, fetal biometric (biparietal diameter (BPD), head circumference, abdominal circumference (AC), femur length (FL) and estimated fetal weight) and amniotic-fluid (amniotic-fluid index (AFI) and maximum vertical pocket (MVP)) measurements were obtained by two experienced sonographers or physicians, blinded to gestational age and each other's measurements. Differences in measurements between observers were expressed as gestational age-specific Z-scores. The interobserver intraclass correlation coefficient (ICC) and Cronbach's reliability coefficient (CRC) were calculated. Bland-Altman analysis was used to assess the degree of reproducibility. RESULTS: In total, 110 women were enrolled prospectively (including 1320 measurements obtained by 17 sonographers or physicians). Twenty (18.2%) women had normal BMI, 30 (27.3%) women were overweight, 30 (27.3%) women were obese and 30 (27.3%) women were morbidly obese. Except for AFI (ICC, 0.65; CRC, 0.78) and MVP (ICC, 0.49; CRC, 0.66), all parameters had a very high level of interobserver reproducibility (ICC, 0.72-0.87; CRC, 0.84-0.93). When assessing reproducibility according to BMI category, BPD measurements had a very high level of reproducibility (ICC ≥ 0.85; CRC > 0.90) in all groups. The reproducibility of AC and FL measurements increased with increasing BMI, while the reproducibility of MVP measurements decreased. Among the biometric parameters, the difference between the BMI categories in measurement-difference Z-score was significant only for FL. Interobserver differences for biometric measurements fell within the 95% limits of agreement. CONCLUSION: Obesity does not seem to impact negatively on the reproducibility of ultrasound measurements of fetal biometric parameters when undertaken by experienced sonographers or physicians who commonly assess overweight, obese and morbidly obese women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Líquido Amniótico/diagnóstico por imagem , Biometria/métodos , Índice de Massa Corporal , Obesidade Materna/diagnóstico por imagem , Ultrassonografia Pré-Natal/estatística & dados numéricos , Adulto , Feminino , Idade Gestacional , Humanos , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Obesidade Materna/fisiopatologia , Obesidade Mórbida/diagnóstico por imagem , Obesidade Mórbida/fisiopatologia , Variações Dependentes do Observador , Sobrepeso/diagnóstico por imagem , Sobrepeso/fisiopatologia , Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Método Simples-CegoRESUMO
OBJECTIVE: We sought to develop a model to calculate the likelihood of vaginal delivery in nulliparous women undergoing induction at term. STUDY DESIGN: We obtained data from the Consortium on Safe Labor by including nulliparous women with term singleton pregnancies undergoing induction of labor at term. Women with contraindications for vaginal delivery were excluded. A stepwise logistic regression analysis was used to identify the predictors associated with vaginal delivery by considering maternal characteristics and comorbidities and fetal conditions. The receiver operating characteristic curve, with an area under the curve (AUC) was used to assess the accuracy of the model. RESULTS: Of 10,591 nulliparous women who underwent induction of labor, 8,202 (77.4%) women had vaginal delivery. Our model identified maternal age, gestational age at delivery, race, maternal height, prepregnancy weight, gestational weight gain, cervical exam on admission (dilation, effacement, and station), chronic hypertension, gestational diabetes, pregestational diabetes, and abruption as significant predictors for successful vaginal delivery. The overall predictive ability of the final model, as measured by the AUC was 0.759 (95% confidence interval, 0.749-0.770). CONCLUSION: We identified independent risk factors that can be used to predict vaginal delivery among nulliparas undergoing induction at term. Our predictor provides women with additional information when considering induction.
Assuntos
Cesárea/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Paridade , Adulto , Feminino , Humanos , Trabalho de Parto Induzido/efeitos adversos , Modelos Logísticos , Nomogramas , Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Nascimento a Termo , Falha de Tratamento , Estados Unidos , Adulto JovemRESUMO
OBJECTIVES: To estimate the incidence and risk of complications associated with a fetal scalp electrode and to determine whether its application in the setting of operative vaginal delivery was associated with increased neonatal morbidity. DESIGN: Retrospective cohort study. SETTING: Twelve clinical centers with 19 hospitals across nine American Congress of Obstetricians and Gynecologists US districts. POPULATION: Women in the USA. METHODS: We evaluated 171 698 women with singleton deliveries ≥ 23 weeks of gestation in a secondary analysis of the Consortium on Safe Labor study between 2002 and 2008, after excluding conditions that precluded fetal scalp electrode application such as prelabour caesarean delivery. Secondary analysis limited to operative vaginal deliveries ≥ 34 weeks of gestation was also performed. MAIN OUTCOME MEASURES: Incidences and adjusted odds ratios with 95% confidence intervals of neonatal complications were calculated, controlling for maternal characteristics, delivery mode and pregnancy complications. RESULTS: Fetal scalp electrode was used in 37 492 (22%) of deliveries. In non-operative vaginal delivery, fetal scalp electrode was associated with increased risk of injury to scalp due to birth trauma (1.2% versus 0.9%; adjusted odds ratios 1.62; 95% confidence intervals 1.41-1.86) and cephalohaematoma (1.0% versus 0.9%; adjusted odds ratios 1.57; 95% confidence intervals 1.36-1.83). Neonatal complications were not significantly different comparing fetal scalp electrode with vacuum-assisted vaginal delivery and vacuum-assisted vaginal delivery alone or comparing fetal scalp electrode with forceps-assisted vaginal delivery and forceps-assisted vaginal delivery alone. CONCLUSIONS: We found increased neonatal morbidity with fetal scalp electrode though the absolute risk was very low. It is possible that these findings reflect an underlying indication for its use. Our findings support the use of fetal scalp electrodes when clinically indicated. TWEETABLE ABSTRACT: Neonatal risks associated with fetal scalp electrode use were low (injury to scalp 1.2% and cephalohaematoma 1.0%).
Assuntos
Traumatismos do Nascimento/etiologia , Cardiotocografia/instrumentação , Parto Obstétrico/efeitos adversos , Eletrodos/efeitos adversos , Couro Cabeludo/lesões , Adulto , Traumatismos do Nascimento/epidemiologia , Cardiotocografia/efeitos adversos , Parto Obstétrico/métodos , Feminino , Humanos , Incidência , Recém-Nascido , Razão de Chances , Gravidez , Estudos Retrospectivos , Couro Cabeludo/embriologia , Estados Unidos/epidemiologiaRESUMO
Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI (20 to < 25 kg/m2), and high BMI (≥ 25 kg/m2). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).
Assuntos
Aborto Espontâneo/epidemiologia , Índice de Massa Corporal , Parto Obstétrico/estatística & dados numéricos , Diabetes Mellitus Tipo 1 , Pré-Eclâmpsia/epidemiologia , Gravidez em Diabéticas , Nascimento Prematuro/epidemiologia , Descolamento Prematuro da Placenta/terapia , Adulto , Peso Corporal , Diabetes Mellitus Tipo 1/sangue , Emergências/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Gravidez , Gravidez em Diabéticas/sangue , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Acute kidney injury (AKI) is a common medical complication after myeloablative allogeneic stem cell transplantation (SCT). We have previously performed a retrospective analysis of AKI after cord blood transplantation (CBT) in adults, and found that the maximum of vancomycin (VCM) trough levels were significantly higher in patients with AKI. Following these results, we have monitored VCM serum trough concentrations more strictly, to not exceed 10.0 mg/L, since 2008. METHODS: In this report, we performed an analysis of AKI in a new group of 38 adult patients with hematological malignancies treated with unrelated CBT after myeloablative conditioning between January 2008 and July 2011. RESULTS: Cumulative incidence of AKI at day 100 after CBT was 34% (95% confidence interval 19-50). The median of the maximum value of VCM trough was 8.8 (4.5-12.2) mg/L. In multivariate analysis, no factor was associated with the incidence of AKI. No transplant-related mortality was observed. The probability of disease-free survival at 2 years was 83%. CONCLUSION: These findings suggest that strict monitoring of VCM serum trough concentrations has a beneficial effect on outcomes of CBT.
Assuntos
Injúria Renal Aguda/etiologia , Antibacterianos/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Monitoramento de Medicamentos , Vancomicina/efeitos adversos , Injúria Renal Aguda/metabolismo , Adolescente , Adulto , Antibacterianos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Vancomicina/farmacocinética , Adulto JovemAssuntos
Diabetes Gestacional/epidemiologia , Gravidez em Diabéticas/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Análise Multivariada , Gravidez , Pontuação de Propensão , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.
Assuntos
Defecação/fisiologia , Fator de Crescimento Insulin-Like I/análise , Hormônios Peptídicos/sangue , Acilação , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Glicemia/análise , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Grelina , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Leptina/sangue , MasculinoRESUMO
AML1-MTG8 generated by t(8;21) contributes to leukemic transformation, but additional events are required for full leukemogenesis. We examined whether mutations in the receptor tyrosine kinase (RTK) pathway could be the genetic events that cause acute myeloblastic leukemia (AML) harboring t(8;21). Mutations in the second tyrosine kinase domain, juxtamembrane (JM) domain and exon 8 of the C-KIT gene were observed in 10, one and three of 37 AML patients with t(8;21), respectively. Three patients showed an internal tandem duplication in the JM domain of the FLT3 gene. One patient had a mutation in the K-Ras gene at codon 12. As the occurrence of these mutations was mutually exclusive, a total of 18 (49%) patients showed mutations in the RTK pathway. These results suggest that activating mutations in the RTK pathway play a role in part as an additional event leading to the development of t(8;21) AML. The 6-year cumulative incidence of relapse in patients with RTK pathway mutations was 79.8%, compared with 13.5% in patients lacking such mutations (P=0.0029). Furthermore, the 6-year relapse-free survival in patients with mutations was 18% compared to 60% in those without mutations (P=0.0340), indicating that RTK mutations are associated with the clinical outcome in t(8;21) AML.
Assuntos
Leucemia Mieloide Aguda/genética , Mutação , Receptores Proteína Tirosina Quinases/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Intervalo Livre de Doença , Feminino , Genes ras , Humanos , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptores Proteína Tirosina Quinases/metabolismo , Recidiva , Sequências de Repetição em Tandem , Translocação Genética , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fmsRESUMO
OBJECTIVE: To investigate the contributions of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to the increase in skeletal muscle blood flow (MBF) observed following manual acupuncture (MA) stimulation in rats. METHODS: Male Sprague-Dawley rats were used as experimental animals (300-370â g, n=40). MA was applied to the right tibialis anterior muscle (TA) for 1â min using a stainless steel acupuncture needle. In eight rats, high-performance liquid chromatography with the microdialysis technique was used to measure local extracellular concentrations of ATP, ADP, adenosine monophosphate (AMP), and adenosine in the TA. In the remaining 32 rats, fluorescent microspheres (15â µm in diameter) were used to measure MBF in the TA following pre-treatment with either the P2 receptor antagonist suramin (100â mg/kg intra-arterially) or saline (control) (n=16 each). Rats receiving MA (Suramin+MA and Saline+MA groups, n=8 each) were compared with untreated rats (Suramin and Saline groups, n=8). RESULTS: MA significantly increased the local extracellular concentration of ATP, ADP, and adenosine (p<0.05, before MA vs 30â min after MA). In addition, MA significantly increased MBF in rats pre-treated with saline or suramin (p<0.01, Saline vs Saline+MA; p<0.05, Suramin vs Suramin+MA, respectively). However, suramin significantly suppressed this MA-induced increase in MBF (p<0.05, Saline+MA vs Suramin+MA). CONCLUSIONS: These results suggest that both ATP and ADP partially contribute to the MA-induced increase in MBF via P2 receptors. However, further studies are needed to clarify the contributions of other vasodilators.
Assuntos
Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Músculo Esquelético/irrigação sanguínea , Terapia por Acupuntura , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Microdiálise , Músculo Esquelético/metabolismo , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo RegionalRESUMO
Diuretic activities of xanthine or nonxanthine adenosine antagonists and their ameliorative effects against glycerol-induced acute renal failure in rats were investigated in order to clarify the physiological and pathological function of adenosine receptors in the kidney. Diuretic and natriuretic activities of a variety of adenosine antagonists clarified systematically for the first time that the blockade of A1 receptors is more important than that of A2 receptors in sodium and water excretion and support the hypothesis that endogenous intrarenal levels of adenosine directly enhance tubular sodium readsorption. Studies of structure-activity relationships of 8-substituted xanthines in the acute renal failure demonstrated that the activation of adenosine A1 receptor was an important factor in developing such a renal failure. A series of 8-(3-noradamantyl)xanthines exhibited the extremely potent diuretic and natriuretic activities (24; 2.5 micrograms/kg, po, the ratio of urinary excretion value in treated rats to urinary excretion value in control rats = 1.69, the ratio of Na+/K+ in treated rats to Na+/K+ in control rats = 1.76) and potent ameliorative effects against glycerol-induced acute renal failure (24; 10 micrograms/kg, ip, 55% inhibition). From our detailed studies of structure-activity relationships, we can speculate that some tissue differences of the adenosine A1 receptor might exist between kidney and brain and sites of action for adenosine antagonists could be different between two renal pharmacological assays. 1,3-Dipropyl-8-(3-noradamantyl)xanthine, KW-3902 (24), was chosen for further studies and is under development as a drug for treating the acute renal failure.
Assuntos
Injúria Renal Aguda/prevenção & controle , Adenosina/antagonistas & inibidores , Diuréticos/farmacologia , Xantinas/farmacologia , Animais , Cátions Monovalentes , Diuréticos/metabolismo , Diuréticos/uso terapêutico , Masculino , Potássio/urina , Ensaio Radioligante , Ratos , Ratos Endogâmicos , Receptores Purinérgicos/metabolismo , Sódio/urina , Relação Estrutura-Atividade , Xantinas/metabolismoRESUMO
In order to develop new oral bronchodilators, a series of novel imidazol[4,5-c][1,8]naphthyridin-4(5H)-ones 5 were designed and synthesized. Some of these new heterocycles exhibited more potent bronchodilator activity in vitro and in vivo than theophylline. With respect to modification at the 5-position, both phenyl and n-butyl substitution produced potent activity. Though bulk tolerance at N-3 is observed with short and small lipophilic groups, any substitution at the other positions and transformations of the parent skeleton eliminated activity. Thus 5-phenyl-1H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (23) (KF17625), which satisfied these conditions, was selected for further studies (antigen inhalation-induced bronchospasm model; minimum effective dose (MED) = 1 mg/kg, po; antigen-induced contraction of trachea (the Schultz-Dale reaction), IC50 = 2.2 microM). Compound 23 inhibited carbachol-, histamine-, or leukotriene D4-induced contraction and relaxed spontaneous tone in guinea pig isolated tracheal preparations with, 4- to 16-fold greater potency than aminophylline. Thus it appeared to relax directly the airway smooth muscle. 23 did not have any influence on adenosine binding at 10 microM, but inhibited canine tracheal phosphodiesterase (PDE) IV (IC50 = 12 microM) and concanavalin-A-induced histamine release from rat mast cells (44% inhibition at 10 microM). Although the detailed mechanisms of these compounds remain to be elucidated, this series of novel tricyclic heterocycles represents a new class of bronchodilator.
Assuntos
Broncodilatadores/síntese química , Imidazóis/síntese química , Naftiridinas/síntese química , Animais , Broncodilatadores/química , Broncodilatadores/farmacologia , Interações Medicamentosas , Cobaias , Imidazóis/química , Imidazóis/farmacologia , Masculino , Camundongos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Naftiridinas/química , Naftiridinas/farmacologia , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/farmacologia , Relação Estrutura-Atividade , Traqueia/efeitos dos fármacosRESUMO
To clarify the behavioral and pathological features of spontaneous scratching of NC mice with mite-induced chronic dermatitis, we investigated the spontaneous and pruritogen-evoked scratching of NC mice. Although the frequency of scratching of NC mouse did not increase under specific pathogen-free environment, it gradually and markedly increased from 3 to 6 weeks after transfer to conventional environment. The onset of increase in spontaneous scratching was similar to that of dermatitis development and the elevation of plasma concentration of immunoglobulin E. At chronic stage (16 weeks after environment change), the frequency of spontaneous scratching was roughly parallel to the degree of dermatitis, but not to the plasma concentration of immunoglobulin E. The spontaneous scratching of NC mice with dermatitis was inhibited by distraction and the opioid antagonist naltrexone, suggesting that the scratching is itch-associated response. An intradermal injection of serotonin, but not histamine and substance P, elicited scratching of the injected site. Methysergide and cyproheptadine inhibited the serotonin-induced scratching but not spontaneous scratching. The results suggest that marked elevation of plasma immunoglobulin E is not always the cause of spontaneous itch-associated response of NC mice with dermatitis. Serotonin, histamine and substance P may not play an important role in spontaneous itch-scratch response at a chronic stage.
Assuntos
Dermatite/complicações , Dermatite/imunologia , Ácaros/imunologia , Prurido/etiologia , Animais , Atenção , Doença Crônica , Dermatite/sangue , Dermatite/patologia , Feminino , Histamina/farmacologia , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Prurido/fisiopatologia , Prurido/psicologia , Serotonina/farmacologia , Substância P/farmacologiaRESUMO
We investigated the effects of KF19514 (5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4 (5H)-one) on bronchoconstriction and allergic inflammation in guinea pigs and on tumor necrosis factor-alpha production in mice. KF19514 inhibited phosphodiesterase 4 (IC50 = 0.40 microM) and phosphodiesterase 1 (IC50 = 0.27 microM) derived from canine tracheal smooth muscles. KF19514 relaxed contracted tracheal smooth muscle and had a potent inhibitory effect on antigen-induced bronchoconstriction (EC50 = 0.058 microM) in vitro. Intravenous administration of KF19514 inhibited histamine-induced bronchoconstriction (ID50 = 2.8 microg/kg i.v.). Moreover, oral administration of KF19514 inhibited anaphylactic bronchoconstriction (ID50 = 0.2 mg/kg p.o.), and eosinophil infiltration in airway stimulated with platelet-activating factor (PAF) or antigen. KF19514 also produced a significant inhibition of tumor necrosis factor-alpha production in mice (ID50 = 0.023 mg/kg p.o.). Finally, KF19514 completely inhibited antigen-induced hyperreactivity at 0.1 mg/kg p.o. These results demonstrate that KF19514 may have efficacy in the treatment of asthma.
Assuntos
Anti-Inflamatórios/farmacologia , Broncodilatadores/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Naftiridinas/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Anafilaxia/tratamento farmacológico , Animais , Antígenos/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Broncoconstrição/efeitos dos fármacos , Broncoconstrição/imunologia , Cães , Eosinófilos/efeitos dos fármacos , Cobaias , Histamina/farmacologia , Hipersensibilidade/imunologia , Técnicas In Vitro , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Coelhos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In this study, the effect of traditional Japanese (Chinese) medicine, Hochu-ekki-to, HOT (Chinese name: Bu-zhong-yi-qi-tang), on the susceptibility against Listeria monocytogenes in postneonatal infant mice was examined. Numbers of bacteria in infant mice (infected at 4 weeks of age) were significantly higher than those in adult mice (infected at 8 weeks of age) on day 3 (non-specific resistance phase) and day 5 (specific resistance phase) after infection. Oral administration of 1,000 mg/kg of HOT for 7 days to infant mice reduced bacterial numbers in the liver and spleen at 5 days after the infection. The amount of IFN-gamma and the number of IFN-gamma-producing CD4+ T cells were lower in infant mice than adult mice but those in infant mice enhanced by HOT treatment. HOT also enhanced the antigen-presenting function along with the expression of MHC class II in infant macrophages induced by heat-killed L. monocytogenes. Further, HOT enhanced the IFN-gamma production from infant CD4+ T cells independent of the deficiency in the antigen-presenting function. These findings suggest that HOT induced simultaneously functional maturation of both infant antigen-presenting cells and T cells, and consequently developed an anti-listerial Th1 response.
Assuntos
Animais Recém-Nascidos/fisiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Listeriose/prevenção & controle , Fitoterapia , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos CD4/imunologia , Contagem de Células , Contagem de Colônia Microbiana , Feminino , Interferon gama/biossíntese , Listeriose/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan, HMG), a traditional Japanese herbal medicine, has been used for disorders accompanying aging. Oral administration of HMG from 8 to 16 weeks of age to MRL/lpr mice as a lupus-like autoimmune model ameliorated significantly some nephritis parameters, proteinuria and immune complex deposition in the kidney. Further, HMG reduced significantly the degree of lymphadenopathy and the serum level of immunoglobulin (Ig) G2a anti-dsDNA specific auto-antibody, even at 12 weeks of age. Simultaneously, interferon (IFN)-gamma production from anti-CD3 stimulated B220- T cells was suppressed by HMG, whereas interleukin (IL)-4 production was promoted. Examination of cytokine mRNA expressions in CD4 positive cells showed clearly that T cell differentiation was shifted from T helper (Th)1 to Th2 predominance by HMG. Furthermore, we demonstrated that HMG suppressed IL-12 mRNA expression in spleen cells which is a marker of Th1 predominance in MRL/lpr mice. These results suggested that HMG modulated an imbalance toward Th1 predominance in MRL/lpr mice through inhibition of IL-12 production and ameliorated autoimmune disorders.
Assuntos
Adjuvantes Imunológicos/farmacologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Animais , Anticorpos Antinucleares/sangue , Doenças Autoimunes/genética , Sequência de Bases , Citocinas/biossíntese , Citocinas/genética , Primers do DNA/genética , Feminino , Imunoglobulina G/biossíntese , Interleucina-12/genética , Japão , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Doenças Linfáticas/tratamento farmacológico , Doenças Linfáticas/genética , Doenças Linfáticas/imunologia , Camundongos , Camundongos Endogâmicos MRL lpr , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
The susceptibility to oral tolerance in post-neonatal infant mice and the effect of a herbal drug, Hochu-ekki-to (HOT), on the susceptibility were investigated. To induce oral tolerance induction, infant and adult mice at 4 and 8 weeks of age, respectively, were orally administered a single high dose of OVA before an intraperitoneal immunization with OVA adsorbed on aluminum hydroxide. HOT (1000 mg/kg) was administered orally for 7 days before the induction. HOT significantly decreased the serum levels of OVA-specific IgE and IgG1 and the antigen-specific proliferation of spleen cells in infant mice, both of which were greatly enhanced compared to in adult mice. HOT increased the number of both CD4+ T cells and antigen-presenting cells expressing MHC class II as well as costimulatory molecules (CD40, CD80 and/or CD86) in the Peyer's patch (PP) of infant mice, which had fewer cells than adult mice. In the PP, moreover, HOT augmented the IL-12p40 mRNA expression and spontaneous or CD40-stimulated IL-12 production, and increased the number of CD4+ cells expressing CD40 ligand, which is up regulated by IL-12. These results suggest that HOT increases the number and improves the function of PP cells that are fully susceptible to the induction of oral tolerance.
Assuntos
Adjuvantes Imunológicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Tolerância Imunológica/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Feminino , Interleucina-12/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/fisiologia , Subpopulações de Linfócitos T/efeitos dos fármacosRESUMO
To determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to, HOT), for the control of allergic disease, we examined the effects of oral administration of HOT on a murine model of asthma allergic responses. When oral administration of HOT was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. The serum levels of OVA-specific immunoglobulin (Ig)E and IgG1 were significantly decreased, whereas the level of OVA-specific IgG2a was increased. Interleukin (IL)-4 production by spleen T cells in response to OVA was significantly suppressed, while Interferon (IFN)-gamma production was increased in mice treated with HOT in the induction phase. On the other hand, HOT given in the eliciting phase induced a predominant Th2 response with increased IgE production in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of HOT dichotomously modulates allergic inflammation in a murine model for asthma, thus offering a different approach for the treatment of allergic disorders.
Assuntos
Asma/tratamento farmacológico , Asma/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Administração Oral , Animais , Asma/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interferon gama/biossíntese , Interleucina-4/biossíntese , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
AIM: To show characteristic ocular surface findings caused by conjunctivochalasis (CCh) in dry eye patients with or without aqueous tear deficiency (ATD). DESIGN: Comparative non-interventional cases. PATIENTS AND METHODS: Clinical data of five ATD patients without CCh (group A), eight CCh patients with ATD (group B), and eight CCh patients without ATD (group C) were retrospectively reviewed. Presence or absence of CCh was determined by fluorescein staining to outline tear meniscus and conjunctival folds with an enhancing filter. Dry eye symptoms, history of subconjunctival haemorrhage, meibum expression, tear break up time, fluorescein and rose bengal staining, and fluorescein clearance test, and other abnormal ocular surface findings were measured. RESULTS: CCh patients were significantly older (p = 0.001). In pure ATD, the principal symptom of dryness became worse as the day progressed. In contrast, blurry vision, burning sensation, and dryness became worse during reading in all CCh patients (p = 0.0008) or worse in the morning upon awakening in the majority patients with CCh only (p = 0.02). Besides the interpalpebral exposure, which was noted in ATD, positive fluorescein or rose bengal staining was noted in the redundant conjunctival folds and the non-exposure zone in CCh (p = 0.0008). Redundant conjunctival folds were present in both lower and upper bulbar conjunctiva, obliterating both lower and upper tear meniscuses, and spatially correlated with anterior migration of the mucocutaneous junction in CCh. Delayed tear clearance was significantly more prevalent in CCh than ATD (p = 0.0008). Vigorous blinking worsened in CCh but not in ATD (p = 0.0008). Lacrimal puncta were swollen in groups B and C, but not in group A (p = 0.04). CONCLUSIONS: CCh is not restricted to the lower bulbar conjunctiva, and contributes to pathogenesis of dry eye by obliterating both lower and upper tear meniscus, causing unstable tear film and by creating delayed tear clearance. Dry eye symptoms were worsened by downgaze during reading and by vigorous blinking. Other characteristic signs including subconjunctival haemorrhage, swollen puncta, anterior migration of the mucocutaneous junction, and patterns of dye staining also help distinguish dry eye associated with CCh from that caused by ATD alone.
Assuntos
Envelhecimento/fisiologia , Túnica Conjuntiva/patologia , Síndromes do Olho Seco/patologia , Lágrimas/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Corantes , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rosa BengalaRESUMO
A complex of the new antitumor antibiotics (WF-1360, WF-1360A, B, C, D, E and F) was produced by Rhizopus sp. No. F-1360. Structural studies of these compounds suggested that they were novel 16-membered-ring lactones having an oxazole ring in their structures. WF-1360 was found to be identical with rhizoxin (1) and WF-1360B, C, E and F were determined to be homologues of 1 with structures 2, 3, 4 and 5, respectively. These compounds were cytotoxic when tested on P388 leukemia cells in vitro. WF-1360 was highly active against leukemia L1210 and melanoma B16. They also exhibited potent antifungal activities, but weak antimicrobial activities against some Gram-positive or negative bacteria.
Assuntos
Antibióticos Antineoplásicos/isolamento & purificação , Rhizopus/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/toxicidade , Bactérias/efeitos dos fármacos , Fenômenos Químicos , Química , Feminino , Fermentação , Lactonas/isolamento & purificação , Lactonas/farmacologia , Leucemia L1210/tratamento farmacológico , Macrolídeos , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos EndogâmicosRESUMO
PURPOSE: A significant correlation between the magnitude of linear vection and the degree of body sway induced by a visual stimulus perceived as moving in depth was previously described (Jpn J Physiol 49: 417-424, 1999). The purpose of this study was to examine the role of the central and peripheral visual fields in inducing vection and body sway. METHODS: Ten healthy volunteer students who had no vestibular or neurological disorders served as subjects. A depth optokinetic stimulus (DOKS) was projected onto a head-mounted display (HMD) and was perceived to move in depth. Different amounts of the central or peripheral visual field were masked independently. The magnitude of the linear vection induced by the DOKS was evaluated by verbal assessment and compared with the magnitude of induced body sway. Body sway was monitored by a video-motion-analyzer that recorded the movement of the head, shoulder, hip, knee and ankle. RESULTS: The magnitude of vection was correlated with the frequency of DOKS and also with the amplitude of body sway (r = 0.74). When the central visual field was restricted by 10 to 30%, there was almost no change in the induced body sway and vection. However, when central occlusion was greater than 40%, depth perception and induced body movement were greatly reduced. With increasing amounts of peripheral field occlusion from 50 to 90%, there was a greater reduction of both vection and body sway. CONCLUSION: Vection is strongly correlated with body movement, and vection and body sway were more dependent on stimulation of the peripheral visual field.